Abstract
Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 μg/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (≤85 μg/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had >50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4052-4058 |
| Number of pages | 7 |
| Journal | Cancer Research |
| Volume | 51 |
| Issue number | 15 |
| State | Published - Aug 1 1991 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Phase I immunotoxin trial in patients with B-cell lymphoma. / Vitetta, Ellen S.; Stone, Marvin; Amlot, Peter; Fay, Joseph; May, Richard; Till, Mark; Newman, Joe; Clark, Patty; Collins, Robert; Cunningham, D.; Ghetie, Victor; Uhr, Jonathan W.; Thorpe, Philip E.
In: Cancer Research, Vol. 51, No. 15, 01.08.1991, p. 4052-4058.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phase I immunotoxin trial in patients with B-cell lymphoma
AU - Vitetta, Ellen S.
AU - Stone, Marvin
AU - Amlot, Peter
AU - Fay, Joseph
AU - May, Richard
AU - Till, Mark
AU - Newman, Joe
AU - Clark, Patty
AU - Collins, Robert
AU - Cunningham, D.
AU - Ghetie, Victor
AU - Uhr, Jonathan W.
AU - Thorpe, Philip E.
PY - 1991/8/1
Y1 - 1991/8/1
N2 - Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 μg/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (≤85 μg/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had >50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.
AB - Fifteen patients with refractory B-cell lymphoma were treated in a Phase I dose escalation clinical trial with a highly potent immunotoxin consisting of the Fab' fragment of a monoclonal anti-CD22 antibody (RFB4) coupled to chemically deglycosylated ricin A chain. All patients had low, intermediate, or high grade non-Hodgkin's lymphoma. The immunotoxin was administered i.v. in two to six doses at 48-h intervals. The peak serum concentration and the t1/2 were not dose dependent among patients and averaged 1.3 μg/ml and 86 min, respectively. Three patients made antibody against A chain, and a fourth made antibody against both A chain and mouse immunoglobulin. Antibody responses were low (≤85 μg/ml) in three patients and were not detected until 1 mo after treatment. The maximum tolerated dose of the immunotoxin was 75 mg/m2. Dose-related toxicities included vascular leak syndrome, fever, anorexia, and myalgia. Dose-limiting toxicities included pulmonary edema and/or effusion, expressive aphasia, and rhabdomyolysis (resulting in reversible kidney failure). There was no evidence of liver dysfunction. Partial responses were achieved in 38% of evaluable patients, and in those patients who had >50% CD22+ tumor cells, 50% of the patients achieved a partial response. Clinical responses were not related to tumor grade and were generally transient, lasting between 1 and 4 mo.
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M3 - Article
VL - 51
SP - 4052
EP - 4058
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 15
ER -